Biopharmaceutical synthesis needs downstream processing for purification of biopharmaceutical products to remove contaminants that are undesirable. In biopharmaceutical synthesis, contaminants may include: host cell proteins, host cell nucleic acids, endotoxins (in the case of bacterial production systems), viruses (in the case of mammalian production systems), misfolded proteins, protein-aggregates and components that leach from chromatographic media. Various chromatographic techniques are typically used for removing the contaminants and affinity chromatography has been a successful attempt for its high specificity, selectivity and resolution.
Affinity chromatography is an effective initial step, following protein production and purification, however, cost and stability of affinity chromatography media, recovery of active product and predictability of optimal process conditions need radical improvement. Binding element, such as, affinity ligands, such as antibodies are valued for their high selectivity and affinity, however, the stability of the molecules due to their size and complex structure is an issue. Engineered protein binders have proved to be successful as affinity ligands for their small size, stability, and ease of synthesis in microbial production systems, however these binders might be unsuitable for therapeutic applications because of their potential immunogenicity. The protein based binders are generally expensive, and are not suitable for repeated use.
Binding-elements that offer reduced cost, better stability, high selectivity and specificity to target and fit to both the single-use and multiple use paradigms are highly desirable. Nucleic acid, namely DNA and RNA based binding-elements, such as aptamers have been developed that show enhanced stability and fit both the single-use and multi-use paradigms. An alternative method for using the binding-elements to identify and recover target efficiently under mild conditions, which ensures maintaining structural and functional integrity of the target molecule, is a long felt need.